Our over-all objective is to elucidate factors which lead to the development of hypertriglyceridemia and atherosclerosis in diabetes. We shall focus our attention on the hypersecretion of very low-density lipoproteins by the liver's Golgi apparatus in animals in which hyperlipemia seems to result from over-production of lipoproteins by the liver under the influence of dietary carbohydrate and insulin. Radioactive precursors of very low-density lipoproteins will be injected or fed to rats and mice (control, insulin-treated-alloxan-diabetic, and obese-hyperglycemic, hyperinsulinemic mice (ob/ob) and rats (Zucker). Incorporation into radioactive triglycerides in various intracellular compartments of the liver and the appearance and disappearance from the circulation of radioactive very low-density lipoprotein triglycerides will be followed as a function of time. Particular attention will be paid to the kinetic analysis of rates of de novo fatty acid synthesis, hepatic synthesis of total lipoprotein triglycerides, nascent lipoprotein synthesis and secretion, and intracellular triglyceride (fat droplet) formation analyzed by multicompartmental analysis. Based upon these analyses, further attempts will be made to define the biochemical mechanisms involved in the regulation of hepatic lipoprotein secretion by insulin and dietary carbohydrates in cell-free systems.